Research Paper Volume 11, Issue 23 pp 10902—10922

The long non-coding RNA SNHG12 promotes gastric cancer by activating the phosphatidylinositol 3-kinase/AKT pathway

Rui Zhang 1, *, , Yuan Liu 1, *, , Hui Liu 1, , Wei Chen 1, , Hui-Ning Fan 1, , Jing Zhang 1, , Jin-Shui Zhu 1, ,

  • 1 Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
* Equal contribution

received: May 21, 2019 ; accepted: November 17, 2019 ; published: December 5, 2019 ;

https://doi.org/10.18632/aging.102493
How to Cite

Copyright © 2019 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Long non-coding RNAs contribute to the development of human cancers. We compared the long non-coding RNA levels in gastric cancer (GC) and para-cancerous tissues in the Gene Expression Omnibus, and found that small nucleolar RNA host gene 12 (SNHG12) was upregulated in GC tissues. Fluorescence in situ hybridization confirmed that SNHG12 is overexpressed in GC tissues. We then used data from The Cancer Genome Atlas to assess the association of SNHG12 expression with the clinicopathological characteristics and prognosis of GC patients and found that higher SNHG12 expression was associated with a greater tumor invasion depth and poorer survival. In vitro, silencing SNHG12 suppressed GC cell proliferation, migration and invasion, but induced apoptosis and cell cycle arrest. Overexpressing SNHG12 had the opposite effects. In xenografted mice, knocking down SNHG12 reduced GC tumor growth. Taken together, cancer pathway microarray and bioinformatics analyses, RNA pulldown assays, Western blotting and immunohistochemistry revealed that SNHG12 induces GC tumorigenesis by activating the phosphatidylinositol 3-kinase/AKT pathway. SNHG12 may thus be a useful marker for predicting poor survival in GC patients.

Abbreviations

LncRNA: long non-coding RNA; SNHG12: small nucleolar RNA host gene 12; FISH: fluorescence in situ hybridization; CCK-8: cell counting kit-8; GC: gastric cancer; TCGA: The Cancer Genome Atlas; HOTTIP: HOXA transcript at the distal tip; MEG3: maternally expressed 3; ADAMTS9-AS2: ADAMTS9 antisense RNA 2; ZEB2-AS1: ZEB2 antisense RNA 1; GES-1: gastric epithelial cells 1; DAPI: 4′,6-diamidino-2-phenylindole; qRT-PCR: quantitative real-time PCR; NC: negative control; HR: hazard ratio; CI: confidential interval; siRNA: small interfering RNA; PI3K: phosphatidylinositol 3-kinase; AKT: protein kinase B; MEK: mitogen-activated protein kinase kinase; ERK: extracellular signal-regulated kinase; MMP-2: matrix metalloproteinase-2; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; DAVID: Database for annotation, visualization and integrated discovery; HOTAIR: HOX transcript antisense RNA.